Healthy Subjects, Sleep Initiation and Maintenance Disorders
Conditions
Keywords
Zopiclone, Hypnotic, Residual effects, Eszopiclone
Brief summary
This study will explore potential next-day residual effects of a single evening dose of 3mg of the hypnotic, eszopiclone, 7.5mg of zopiclone, and placebo, in healthy adult subjects.
Interventions
DRUGGSK1755165; placebo; zopiclone
Subjects receive either 3mg GSK1755165, matching placebo or 7.5mg zopiclone
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects providing written informed consent.
Exclusion criteria
* Significant medical disorders; * Sleeping difficulties; alcohol and/or substance abuse; * Recent use of psychotropic medications, or need to use them during study; * Very high BMI or very low BMI or bodyweight; * Known hypersensitivity to the study medications or their excipients; * Unwilling or unable to meet certain lifestyle or dietary restrictions during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Tracking Error Assessed During the Continuous Tracking Test (CTT) | 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) | Analysis was performed on the mean of the five assessments conducted 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) The CTT is a task (duration of 8 minutes) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the mean tracking error - the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CTT Mean Reaction Time | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) A further outcome derived from the CTT is a peripheral awareness task where the participant responds to a stimulus presented in the periphery of vision, while simultaneously attending to the tracking test. The mean reaction time, in milliseconds, to these stimuli over the trial period is taken as the response measure for this component of the divided attention task. A lower mean reaction time is indicative of better peripheral awareness. |
| Critical Flicker Fusion Test-Ascending Threshold | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Critical Flicker Fusion (CFF) is a validated cognitive assessment task that provides an index of central nervous system (CNS) activity and attention modulated motion detection. Participants are required to discriminate flicker from fusion, and vice versa, in a set of four light-emitting diodes arranged in a one-centimetre square. These diodes are held in foveal fixation when viewed at a distance of one metre. Individual thresholds are determined on four ascending and four descending scales. The mean of the four ascending presentations give the ascending threshold frequency in hertz. |
| Critical Flicker Fusion Test -Descending Threshold | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four descending presentations from the CFF give the descending threshold frequency in hertz. |
| Critical Flicker Fusion Test-Overall Threshold | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four ascending and four descending presentations of the CFF give the overall threshold frequency in hertz. |
| Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. |
| Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test. |
| Mean Tracking Error (MTE) Assessed During the CTT | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) . The CTT is a task (8 minute duration) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the MTE, the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking. |
| 3-Back Percentage of Correct Responses | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). In 3-back tasks, a comparison is made between the current stimulus and the two before the immediately preceding stimulus. In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 min. The percentage of correct responses is the percentage of correct responses given in 2 min. |
| 1-Back Reaction Time | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. |
| 3-Back Reaction Time | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus. |
| Sedation Score, as Assessed by the Linear Analogue Rating Scales | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | The Linear Analogue Rating Scale (LARS) is used as a measure of the subjective effects of psychoactive drugs. Participants mark a series of 10 cm (100 unit line) analogue scales (1-100, 100 = most impaired) relating to dizzy, clumsy, anxious, relaxed, tired, drowsy, alert, energetic, sad, and depressed, indicating their present feeling with regard to a mid-point, representing their usual state of mind before treatment began. The higher the score, the more impaired the participant feels. The Tiredness, Alertness, Energy, and Drowsiness scores are averaged to derive an overall Sedation score. |
| Mood Score, as Assessed by the Linear Analogue Rating Scales | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Anxiety, Depression, Relaxed, and Sadness scores are averaged to derive an overall Mood score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired. |
| Coordination Score, as Assessed by the Linear Analogue Rating Scales | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Dizziness and Clumsiness scores are averaged to derive an overall Coordination score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired. |
| 1-Back Percentage of Correct Responses | 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) | The N-Back task requires the participant to indicate, using the mouse, whether the current stimulus presented on the screen and the one immediately before it visually match (i.e., one-back). In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 minutes. The percentage of correct responses is the percentage of correct responses given in 2 minutes. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 |
| First Intervention | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Second Intervention | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Second Intervention | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 29.8 years STANDARD_DEVIATION 3.87 |
| Race/Ethnicity, Customized African American/African Heritage | 14 participants |
| Race/Ethnicity, Customized Asian-Central/South Asian Heritage | 6 participants |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 3 participants |
| Race/Ethnicity, Customized Asian-South East Asian Heritage | 5 participants |
| Race/Ethnicity, Customized White | 63 participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 89 | 44 / 88 | 44 / 90 |
| serious Total, serious adverse events | 0 / 89 | 0 / 88 | 0 / 90 |
Outcome results
Primary
Mean Tracking Error Assessed During the Continuous Tracking Test (CTT)
Analysis was performed on the mean of the five assessments conducted 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind) The CTT is a task (duration of 8 minutes) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the mean tracking error - the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking.
Time frame: 7.5, 8, 8.5, 9, and 9.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all subjects who gave informed consent, were randomised, and received at least one dose of double-blind medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Tracking Error Assessed During the Continuous Tracking Test (CTT) | 10.29 pixels | Standard Error 0.625 |
| Eszopiclone | Mean Tracking Error Assessed During the Continuous Tracking Test (CTT) | 12.49 pixels | Standard Error 0.634 |
| Zopiclone | Mean Tracking Error Assessed During the Continuous Tracking Test (CTT) | 13.48 pixels | Standard Error 0.621 |
p-value: 0.26795% CI: [-2.74, 0.76]ANCOVA
Secondary
1-Back Percentage of Correct Responses
The N-Back task requires the participant to indicate, using the mouse, whether the current stimulus presented on the screen and the one immediately before it visually match (i.e., one-back). In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 minutes. The percentage of correct responses is the percentage of correct responses given in 2 minutes.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 1-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 93.5 percentage of responses | Standard Error 1.07 |
| Placebo | 1-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 93.4 percentage of responses | Standard Error 0.92 |
| Placebo | 1-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 93.0 percentage of responses | Standard Error 0.9 |
| Placebo | 1-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 92.9 percentage of responses | Standard Error 1.02 |
| Placebo | 1-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 93.9 percentage of responses | Standard Error 0.95 |
| Placebo | 1-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 93.0 percentage of responses | Standard Error 0.92 |
| Placebo | 1-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 93.6 percentage of responses | Standard Error 1.05 |
| Placebo | 1-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 93.3 percentage of responses | Standard Error 0.97 |
| Placebo | 1-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 94.4 percentage of responses | Standard Error 0.94 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 91.2 percentage of responses | Standard Error 1.02 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 92.2 percentage of responses | Standard Error 0.96 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 92.0 percentage of responses | Standard Error 0.98 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 92.8 percentage of responses | Standard Error 1.06 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 91.6 percentage of responses | Standard Error 1.08 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 92.2 percentage of responses | Standard Error 0.91 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 92.0 percentage of responses | Standard Error 0.95 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 92.6 percentage of responses | Standard Error 0.93 |
| Eszopiclone | 1-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 94.0 percentage of responses | Standard Error 0.92 |
| Zopiclone | 1-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 89.6 percentage of responses | Standard Error 1.05 |
| Zopiclone | 1-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 90.4 percentage of responses | Standard Error 0.95 |
| Zopiclone | 1-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 91.7 percentage of responses | Standard Error 0.94 |
| Zopiclone | 1-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 89.5 percentage of responses | Standard Error 0.97 |
| Zopiclone | 1-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 92.0 percentage of responses | Standard Error 0.91 |
| Zopiclone | 1-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 90.7 percentage of responses | Standard Error 1.01 |
| Zopiclone | 1-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 89.4 percentage of responses | Standard Error 1.07 |
| Zopiclone | 1-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 91.9 percentage of responses | Standard Error 0.92 |
| Zopiclone | 1-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 92.0 percentage of responses | Standard Error 0.9 |
Secondary
1-Back Reaction Time
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 1-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 734.8 milliseconds | Standard Error 16.58 |
| Placebo | 1-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 709.3 milliseconds | Standard Error 16.83 |
| Placebo | 1-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 724.7 milliseconds | Standard Error 16.39 |
| Placebo | 1-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 729.0 milliseconds | Standard Error 16.84 |
| Placebo | 1-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 755.9 milliseconds | Standard Error 17.81 |
| Placebo | 1-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 718.5 milliseconds | Standard Error 16.26 |
| Placebo | 1-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 741.1 milliseconds | Standard Error 17.09 |
| Placebo | 1-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 752.7 milliseconds | Standard Error 16.89 |
| Placebo | 1-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 713.2 milliseconds | Standard Error 15.81 |
| Eszopiclone | 1-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 757.2 milliseconds | Standard Error 16.98 |
| Eszopiclone | 1-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 819.3 milliseconds | Standard Error 17.85 |
| Eszopiclone | 1-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 783.7 milliseconds | Standard Error 16.99 |
| Eszopiclone | 1-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 776.1 milliseconds | Standard Error 17.18 |
| Eszopiclone | 1-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 784.5 milliseconds | Standard Error 16.68 |
| Eszopiclone | 1-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 760.8 milliseconds | Standard Error 16.48 |
| Eszopiclone | 1-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 735.2 milliseconds | Standard Error 15.92 |
| Eszopiclone | 1-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 716.9 milliseconds | Standard Error 16.33 |
| Eszopiclone | 1-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 716.7 milliseconds | Standard Error 16.92 |
| Zopiclone | 1-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 778.7 milliseconds | Standard Error 17.04 |
| Zopiclone | 1-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 840.3 milliseconds | Standard Error 17.75 |
| Zopiclone | 1-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 750.7 milliseconds | Standard Error 15.8 |
| Zopiclone | 1-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 805.8 milliseconds | Standard Error 16.87 |
| Zopiclone | 1-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 720.5 milliseconds | Standard Error 16.78 |
| Zopiclone | 1-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 784.0 milliseconds | Standard Error 16.8 |
| Zopiclone | 1-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 791.1 milliseconds | Standard Error 16.58 |
| Zopiclone | 1-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 741.7 milliseconds | Standard Error 16.22 |
| Zopiclone | 1-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 759.5 milliseconds | Standard Error 16.34 |
Secondary
3-Back Percentage of Correct Responses
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). In 3-back tasks, a comparison is made between the current stimulus and the two before the immediately preceding stimulus. In the versions of the tests used in this study, the stimuli are presented on screen for 500 ms, and the interval between stimuli is 2500 ms, with a ratio of 1:2 of match trials to non-match trials. The duration of the test is 2 min. The percentage of correct responses is the percentage of correct responses given in 2 min.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 3-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 84.6 percentage of responses | Standard Error 1.4 |
| Placebo | 3-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 83.5 percentage of responses | Standard Error 1.55 |
| Placebo | 3-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 82.4 percentage of responses | Standard Error 1.56 |
| Placebo | 3-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 83.3 percentage of responses | Standard Error 1.61 |
| Placebo | 3-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 82.1 percentage of responses | Standard Error 1.6 |
| Placebo | 3-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 83.4 percentage of responses | Standard Error 1.53 |
| Placebo | 3-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 82.6 percentage of responses | Standard Error 1.5 |
| Placebo | 3-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 81.7 percentage of responses | Standard Error 1.44 |
| Placebo | 3-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 82.9 percentage of responses | Standard Error 1.4 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 83.2 percentage of responses | Standard Error 1.45 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 81.1 percentage of responses | Standard Error 1.57 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 80.2 percentage of responses | Standard Error 1.61 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 80.4 percentage of responses | Standard Error 1.41 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 78.9 percentage of responses | Standard Error 1.62 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 81.3 percentage of responses | Standard Error 1.51 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 82.3 percentage of responses | Standard Error 1.56 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 82.0 percentage of responses | Standard Error 1.54 |
| Eszopiclone | 3-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 83.6 percentage of responses | Standard Error 1.41 |
| Zopiclone | 3-Back Percentage of Correct Responses | 10.5 hours post-dose, n=89, 86, 89 | 79.7 percentage of responses | Standard Error 1.5 |
| Zopiclone | 3-Back Percentage of Correct Responses | 9 hours post-dose, n=89, 87, 90 | 77.3 percentage of responses | Standard Error 1.6 |
| Zopiclone | 3-Back Percentage of Correct Responses | 11 hours post-dose, n=89, 87, 90 | 79.8 percentage of responses | Standard Error 1.44 |
| Zopiclone | 3-Back Percentage of Correct Responses | 10 hours post-dose, n=89, 87, 90 | 79.2 percentage of responses | Standard Error 1.52 |
| Zopiclone | 3-Back Percentage of Correct Responses | 11.5 hours post-dose, n=89, 87, 90 | 81.1 percentage of responses | Standard Error 1.39 |
| Zopiclone | 3-Back Percentage of Correct Responses | 9.5 hours post-dose, n=89, 86, 90 | 76.9 percentage of responses | Standard Error 1.59 |
| Zopiclone | 3-Back Percentage of Correct Responses | 7.5 hours post-dose, n=87, 87, 88 | 76.9 percentage of responses | Standard Error 1.4 |
| Zopiclone | 3-Back Percentage of Correct Responses | 8 hours post-dose, n=89, 87, 89 | 76.8 percentage of responses | Standard Error 1.55 |
| Zopiclone | 3-Back Percentage of Correct Responses | 8.5 hours post-dose, n=89, 87, 90 | 78.3 percentage of responses | Standard Error 1.55 |
Secondary
3-Back Reaction Time
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). Reaction time is the time taken to respond to a stimulus.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 3-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 916.9 milliseconds | Standard Error 21.5 |
| Placebo | 3-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 876.2 milliseconds | Standard Error 20.49 |
| Placebo | 3-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 907.4 milliseconds | Standard Error 21.26 |
| Placebo | 3-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 932.9 milliseconds | Standard Error 21.86 |
| Placebo | 3-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 959.5 milliseconds | Standard Error 20.87 |
| Placebo | 3-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 915.3 milliseconds | Standard Error 19.61 |
| Placebo | 3-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 925.9 milliseconds | Standard Error 21.37 |
| Placebo | 3-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 960.0 milliseconds | Standard Error 21.56 |
| Placebo | 3-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 900.3 milliseconds | Standard Error 20.92 |
| Eszopiclone | 3-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 992.1 milliseconds | Standard Error 22.05 |
| Eszopiclone | 3-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 1020.9 milliseconds | Standard Error 20.87 |
| Eszopiclone | 3-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 1018.5 milliseconds | Standard Error 21.62 |
| Eszopiclone | 3-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 997.7 milliseconds | Standard Error 21.49 |
| Eszopiclone | 3-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 1002.2 milliseconds | Standard Error 21.61 |
| Eszopiclone | 3-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 948.7 milliseconds | Standard Error 21.36 |
| Eszopiclone | 3-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 961.5 milliseconds | Standard Error 21.08 |
| Eszopiclone | 3-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 935.5 milliseconds | Standard Error 19.7 |
| Eszopiclone | 3-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 903.2 milliseconds | Standard Error 20.58 |
| Zopiclone | 3-Back Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 1024.2 milliseconds | Standard Error 21.33 |
| Zopiclone | 3-Back Reaction Time | 7.5 hours post-dose, n=87, 87, 88 | 1076.4 milliseconds | Standard Error 20.79 |
| Zopiclone | 3-Back Reaction Time | 10.5 hours post-dose, n=89, 86, 89 | 945.2 milliseconds | Standard Error 20.89 |
| Zopiclone | 3-Back Reaction Time | 8 hours post-dose, n=89, 87, 89 | 1042.2 milliseconds | Standard Error 21.53 |
| Zopiclone | 3-Back Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 934.7 milliseconds | Standard Error 20.39 |
| Zopiclone | 3-Back Reaction Time | 9.5 hours post-dose, n=89, 86, 90 | 978.0 milliseconds | Standard Error 21.81 |
| Zopiclone | 3-Back Reaction Time | 9 hours post-dose, n=89, 87, 90 | 1007.8 milliseconds | Standard Error 21.46 |
| Zopiclone | 3-Back Reaction Time | 11 hours post-dose, n=89, 87, 90 | 940.4 milliseconds | Standard Error 19.54 |
| Zopiclone | 3-Back Reaction Time | 10 hours post-dose, n=89, 87, 90 | 987.5 milliseconds | Standard Error 21.19 |
Secondary
Coordination Score, as Assessed by the Linear Analogue Rating Scales
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Dizziness and Clumsiness scores are averaged to derive an overall Coordination score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 48.60 points on a scale | Standard Error 0.86 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 49.68 points on a scale | Standard Error 0.94 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 50.03 points on a scale | Standard Error 0.92 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 49.37 points on a scale | Standard Error 0.96 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 49.08 points on a scale | Standard Error 0.97 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 49.09 points on a scale | Standard Error 1.13 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 48.97 points on a scale | Standard Error 0.83 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 49.23 points on a scale | Standard Error 0.86 |
| Placebo | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 48.20 points on a scale | Standard Error 0.82 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 48.51 points on a scale | Standard Error 0.84 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 50.33 points on a scale | Standard Error 1.15 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 51.21 points on a scale | Standard Error 0.93 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 49.52 points on a scale | Standard Error 0.87 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 50.38 points on a scale | Standard Error 0.95 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 49.42 points on a scale | Standard Error 0.98 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 49.72 points on a scale | Standard Error 0.97 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 50.68 points on a scale | Standard Error 0.87 |
| Eszopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 47.45 points on a scale | Standard Error 0.83 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 50.27 points on a scale | Standard Error 0.95 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 51.76 points on a scale | Standard Error 0.86 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 49.82 points on a scale | Standard Error 0.81 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 50.40 points on a scale | Standard Error 0.86 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 52.10 points on a scale | Standard Error 0.92 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 49.96 points on a scale | Standard Error 0.83 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 51.41 points on a scale | Standard Error 0.96 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 50.41 points on a scale | Standard Error 0.94 |
| Zopiclone | Coordination Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 52.42 points on a scale | Standard Error 1.13 |
Secondary
Critical Flicker Fusion Test-Ascending Threshold
Critical Flicker Fusion (CFF) is a validated cognitive assessment task that provides an index of central nervous system (CNS) activity and attention modulated motion detection. Participants are required to discriminate flicker from fusion, and vice versa, in a set of four light-emitting diodes arranged in a one-centimetre square. These diodes are held in foveal fixation when viewed at a distance of one metre. Individual thresholds are determined on four ascending and four descending scales. The mean of the four ascending presentations give the ascending threshold frequency in hertz.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 9 hours post-dose, n=89, 87, 90 | 30.10 hertz | Standard Error 0.23 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 30.31 hertz | Standard Error 0.22 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 10 hours post-dose, n=89, 87, 90 | 30.20 hertz | Standard Error 0.24 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 30.18 hertz | Standard Error 0.23 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 30.65 hertz | Standard Error 0.24 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 11 hours post-dose, n=89, 87, 90 | 30.20 hertz | Standard Error 0.23 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 30.27 hertz | Standard Error 0.22 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 8 hours post-dose, n=89, 87, 90 | 30.31 hertz | Standard Error 0.24 |
| Placebo | Critical Flicker Fusion Test-Ascending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 30.26 hertz | Standard Error 0.21 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 29.99 hertz | Standard Error 0.23 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 30.84 hertz | Standard Error 0.24 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 8 hours post-dose, n=89, 87, 90 | 30.30 hertz | Standard Error 0.24 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 29.98 hertz | Standard Error 0.22 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 9 hours post-dose, n=89, 87, 90 | 29.90 hertz | Standard Error 0.23 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 10 hours post-dose, n=89, 87, 90 | 29.91 hertz | Standard Error 0.24 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 29.99 hertz | Standard Error 0.22 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 11 hours post-dose, n=89, 87, 90 | 30.06 hertz | Standard Error 0.23 |
| Eszopiclone | Critical Flicker Fusion Test-Ascending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 30.28 hertz | Standard Error 0.23 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 30.17 hertz | Standard Error 0.22 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 30.93 hertz | Standard Error 0.24 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 30.16 hertz | Standard Error 0.21 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 8 hours post-dose, n=89, 87, 90 | 30.41 hertz | Standard Error 0.24 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 30.56 hertz | Standard Error 0.22 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 30.05 hertz | Standard Error 0.23 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 9 hours post-dose, n=89, 87, 90 | 30.00 hertz | Standard Error 0.23 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 11 hours post-dose, n=89, 87, 90 | 30.04 hertz | Standard Error 0.23 |
| Zopiclone | Critical Flicker Fusion Test-Ascending Threshold | 10 hours post-dose, n=89, 87, 90 | 29.97 hertz | Standard Error 0.23 |
Secondary
Critical Flicker Fusion Test -Descending Threshold
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four descending presentations from the CFF give the descending threshold frequency in hertz.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication.Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 9 hours post-dose, n=89, 87, 90 | 28.07 hertz | Standard Error 0.34 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 28.57 hertz | Standard Error 0.33 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 10 hours post-dose, n=89, 87, 90 | 28.18 hertz | Standard Error 0.34 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 28.19 hertz | Standard Error 0.34 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 29.06 hertz | Standard Error 0.35 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 11 hours post-dose, n=89, 87, 90 | 28.53 hertz | Standard Error 0.34 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 28.42 hertz | Standard Error 0.34 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 8 hours post-dose, n=89, 87, 90 | 28.52 hertz | Standard Error 0.33 |
| Placebo | Critical Flicker Fusion Test -Descending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 28.48 hertz | Standard Error 0.34 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 27.81 hertz | Standard Error 0.35 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 28.37 hertz | Standard Error 0.35 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 8 hours post-dose, n=89, 87, 90 | 27.95 hertz | Standard Error 0.33 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 27.75 hertz | Standard Error 0.35 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 9 hours post-dose, n=89, 87, 90 | 27.64 hertz | Standard Error 0.35 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 10 hours post-dose, n=89, 87, 90 | 27.96 hertz | Standard Error 0.34 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 27.99 hertz | Standard Error 0.34 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 11 hours post-dose, n=89, 87, 90 | 28.03 hertz | Standard Error 0.34 |
| Eszopiclone | Critical Flicker Fusion Test -Descending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 28.69 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 8.5 hours post-dose, n=89, 87, 90 | 27.59 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 7.5 hours post-dose, n=88, 87, 90 | 28.05 hertz | Standard Error 0.35 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 10.5 hours post-dose, n=89, 87, 89 | 28.10 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 8 hours post-dose, n=89, 87, 90 | 27.95 hertz | Standard Error 0.33 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 11.5 hours post-dose, n=89, 87, 90 | 28.48 hertz | Standard Error 0.33 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 9.5 hours post-dose, n=89, 87, 90 | 27.75 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 9 hours post-dose, n=89, 87, 90 | 27.89 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 11 hours post-dose, n=89, 87, 90 | 28.20 hertz | Standard Error 0.34 |
| Zopiclone | Critical Flicker Fusion Test -Descending Threshold | 10 hours post-dose, n=89, 87, 90 | 28.06 hertz | Standard Error 0.34 |
Secondary
Critical Flicker Fusion Test-Overall Threshold
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) The mean of the four ascending and four descending presentations of the CFF give the overall threshold frequency in hertz.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 10.5 hours post-dose, n=89, 87, 89 | 29.38 hertz | Standard Error 0.24 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 7.5 hours post-dose, n=88, 87, 90 | 29.82 hertz | Standard Error 0.26 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 8 hours post-dose, n=89, 87, 90 | 29.41 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 8.5 hours post-dose, n=89, 87, 90 | 29.36 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 9 hours post-dose, n=89, 87, 90 | 29.10 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 9.5 hours post-dose, n=89, 87, 90 | 29.19 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 10 hours post-dose, n=89, 87, 90 | 29.20 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 11 hours post-dose, n=89, 87, 90 | 29.37 hertz | Standard Error 0.25 |
| Placebo | Critical Flicker Fusion Test-Overall Threshold | 11.5 hours post-dose, n=89, 87, 90 | 29.46 hertz | Standard Error 0.24 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 9.5 hours post-dose, n=89, 87, 90 | 28.90 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 10.5 hours post-dose, n=89, 87, 89 | 29.00 hertz | Standard Error 0.24 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 7.5 hours post-dose, n=88, 87, 90 | 29.57 hertz | Standard Error 0.26 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 11 hours post-dose, n=89, 87, 90 | 29.07 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 9 hours post-dose, n=89, 87, 90 | 28.79 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 8 hours post-dose, n=89, 87, 90 | 29.11 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 10 hours post-dose, n=89, 87, 90 | 28.95 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 11.5 hours post-dose, n=89, 87, 90 | 29.50 hertz | Standard Error 0.25 |
| Eszopiclone | Critical Flicker Fusion Test-Overall Threshold | 8.5 hours post-dose, n=89, 87, 90 | 28.86 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 10 hours post-dose, n=89, 87, 90 | 29.02 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 9 hours post-dose, n=89, 87, 90 | 28.96 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 11 hours post-dose, n=89, 87, 90 | 29.14 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 9.5 hours post-dose, n=89, 87, 90 | 28.90 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 11.5 hours post-dose, n=89, 87, 90 | 29.53 hertz | Standard Error 0.24 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 8.5 hours post-dose, n=89, 87, 90 | 28.88 hertz | Standard Error 0.25 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 7.5 hours post-dose, n=88, 87, 90 | 29.45 hertz | Standard Error 0.26 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 10.5 hours post-dose, n=89, 87, 89 | 29.14 hertz | Standard Error 0.24 |
| Zopiclone | Critical Flicker Fusion Test-Overall Threshold | 8 hours post-dose, n=89, 87, 90 | 29.00 hertz | Standard Error 0.24 |
Secondary
CTT Mean Reaction Time
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) A further outcome derived from the CTT is a peripheral awareness task where the participant responds to a stimulus presented in the periphery of vision, while simultaneously attending to the tracking test. The mean reaction time, in milliseconds, to these stimuli over the trial period is taken as the response measure for this component of the divided attention task. A lower mean reaction time is indicative of better peripheral awareness.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication.Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CTT Mean Reaction Time | 10.5 hours post-dose, n=89, 87, 90 | 765.98 milliseconds | Standard Error 10.55 |
| Placebo | CTT Mean Reaction Time | 9 hours post-dose, n=89, 87, 90 | 760.11 milliseconds | Standard Error 10.75 |
| Placebo | CTT Mean Reaction Time | 8 hours post-dose, n=88, 87, 90 | 744.90 milliseconds | Standard Error 10.44 |
| Placebo | CTT Mean Reaction Time | 10 hours post-dose, n=89, 87, 90 | 756.67 milliseconds | Standard Error 10.54 |
| Placebo | CTT Mean Reaction Time | 9.5 hours post-dose, n=89, 87, 90 | 763.65 milliseconds | Standard Error 10.17 |
| Placebo | CTT Mean Reaction Time | 7.5 hours post-dose, n=89, 87, 90 | 746.88 milliseconds | Standard Error 10.36 |
| Placebo | CTT Mean Reaction Time | 11 hours post-dose, n=89, 87, 90 | 762.43 milliseconds | Standard Error 9.88 |
| Placebo | CTT Mean Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 757.72 milliseconds | Standard Error 10.44 |
| Placebo | CTT Mean Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 745.26 milliseconds | Standard Error 9.48 |
| Eszopiclone | CTT Mean Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 750.79 milliseconds | Standard Error 9.52 |
| Eszopiclone | CTT Mean Reaction Time | 7.5 hours post-dose, n=89, 87, 90 | 791.99 milliseconds | Standard Error 10.4 |
| Eszopiclone | CTT Mean Reaction Time | 8 hours post-dose, n=88, 87, 90 | 787.41 milliseconds | Standard Error 10.5 |
| Eszopiclone | CTT Mean Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 793.18 milliseconds | Standard Error 10.51 |
| Eszopiclone | CTT Mean Reaction Time | 9 hours post-dose, n=89, 87, 90 | 802.53 milliseconds | Standard Error 10.81 |
| Eszopiclone | CTT Mean Reaction Time | 9.5 hours post-dose, n=89, 87, 90 | 793.69 milliseconds | Standard Error 10.23 |
| Eszopiclone | CTT Mean Reaction Time | 10 hours post-dose, n=89, 87, 90 | 778.09 milliseconds | Standard Error 10.6 |
| Eszopiclone | CTT Mean Reaction Time | 10.5 hours post-dose, n=89, 87, 90 | 774.06 milliseconds | Standard Error 10.59 |
| Eszopiclone | CTT Mean Reaction Time | 11 hours post-dose, n=89, 87, 90 | 760.29 milliseconds | Standard Error 9.95 |
| Zopiclone | CTT Mean Reaction Time | 10 hours post-dose, n=89, 87, 90 | 792.00 milliseconds | Standard Error 10.48 |
| Zopiclone | CTT Mean Reaction Time | 8.5 hours post-dose, n=89, 87, 90 | 797.92 milliseconds | Standard Error 10.39 |
| Zopiclone | CTT Mean Reaction Time | 7.5 hours post-dose, n=89, 87, 90 | 806.31 milliseconds | Standard Error 10.33 |
| Zopiclone | CTT Mean Reaction Time | 10.5 hours post-dose, n=89, 87, 90 | 779.80 milliseconds | Standard Error 10.51 |
| Zopiclone | CTT Mean Reaction Time | 8 hours post-dose, n=88, 87, 90 | 799.53 milliseconds | Standard Error 10.4 |
| Zopiclone | CTT Mean Reaction Time | 11.5 hours post-dose, n=89, 87, 90 | 766.44 milliseconds | Standard Error 9.44 |
| Zopiclone | CTT Mean Reaction Time | 9.5 hours post-dose, n=89, 87, 90 | 789.63 milliseconds | Standard Error 10.13 |
| Zopiclone | CTT Mean Reaction Time | 9 hours post-dose, n=89, 87, 90 | 811.11 milliseconds | Standard Error 10.69 |
| Zopiclone | CTT Mean Reaction Time | 11 hours post-dose, n=89, 87, 90 | 765.56 milliseconds | Standard Error 9.85 |
Secondary
Mean Tracking Error (MTE) Assessed During the CTT
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind) . The CTT is a task (8 minute duration) of psychomotor function that entails using a slider to keep a cursor in alignment with a moving target on a visual display unit screen. The movement of the target is the function of an irregular sine wave, and cursor accuracy is measured by the MTE, the difference between the centers of target and cursor in pixels, sampled 5 times per second, over the test. Lower scores are indicative of more accurate tracking.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 9 hours post-dose | 11.02 pixels | Standard Error 0.214 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 11.5 hours post-dose | 9.18 pixels | Standard Error 0.523 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 10 hours post-dose | 10.12 pixels | Standard Error 1.057 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 9.5 hours post-dose | 10.44 pixels | Standard Error 1.108 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 7.5 hours post-dose | 10.20 pixels | Standard Error 0.596 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 11 hours post-dose | 10.55 pixels | Standard Error 0.822 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 8.5 hours post-dose | 10.08 pixels | Standard Error 0.917 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 8 hours post-dose | 9.70 pixels | Standard Error 0.83 |
| Placebo | Mean Tracking Error (MTE) Assessed During the CTT | 10.5 hours post-dose | 9.48 pixels | Standard Error 0.757 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 9.5 hours post-dose | 13.50 pixels | Standard Error 1.121 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 7.5 hours post-dose | 12.80 pixels | Standard Error 0.602 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 8 hours post-dose | 12.72 pixels | Standard Error 0.84 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 8.5 hours post-dose | 12.54 pixels | Standard Error 0.928 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 9 hours post-dose | 13.00 pixels | Standard Error 1.229 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 10 hours post-dose | 12.85 pixels | Standard Error 1.069 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 10.5 hours post-dose | 11.38 pixels | Standard Error 0.767 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 11 hours post-dose | 10.86 pixels | Standard Error 0.833 |
| Eszopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 11.5 hours post-dose | 10.06 pixels | Standard Error 0.53 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 8.5 hours post-dose | 12.93 pixels | Standard Error 0.913 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 7.5 hours post-dose | 13.07 pixels | Standard Error 0.592 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 10.5 hours post-dose | 11.84 pixels | Standard Error 0.753 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 8 hours post-dose | 13.15 pixels | Standard Error 0.826 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 11.5 hours post-dose | 10.30 pixels | Standard Error 0.521 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 9.5 hours post-dose | 13.55 pixels | Standard Error 1.101 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 9 hours post-dose | 14.81 pixels | Standard Error 1.208 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 11 hours post-dose | 11.65 pixels | Standard Error 0.818 |
| Zopiclone | Mean Tracking Error (MTE) Assessed During the CTT | 10 hours post-dose | 12.53 pixels | Standard Error 1.051 |
Secondary
Mood Score, as Assessed by the Linear Analogue Rating Scales
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Anxiety, Depression, Relaxed, and Sadness scores are averaged to derive an overall Mood score (as described in Outcome Measure 14). Each item was assessed on a 1-100 point scale, where 100 indicates most impaired.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 48.48 points on a scale | Standard Error 0.74 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 45.63 points on a scale | Standard Error 1.03 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 47.98 points on a scale | Standard Error 0.79 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 48.30 points on a scale | Standard Error 0.75 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 49.19 points on a scale | Standard Error 0.71 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 47.75 points on a scale | Standard Error 0.71 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 47.45 points on a scale | Standard Error 0.85 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 48.88 points on a scale | Standard Error 0.7 |
| Placebo | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 47.57 points on a scale | Standard Error 0.87 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 48.42 points on a scale | Standard Error 0.7 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 48.13 points on a scale | Standard Error 0.72 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 48.42 points on a scale | Standard Error 0.71 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 47.67 points on a scale | Standard Error 0.75 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 47.89 points on a scale | Standard Error 0.76 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 48.25 points on a scale | Standard Error 0.79 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 48.72 points on a scale | Standard Error 0.88 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 47.07 points on a scale | Standard Error 0.86 |
| Eszopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 47.09 points on a scale | Standard Error 1.4 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 48.30 points on a scale | Standard Error 0.69 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 48.03 points on a scale | Standard Error 0.71 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 48.47 points on a scale | Standard Error 0.87 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 49.11 points on a scale | Standard Error 0.7 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 46.08 points on a scale | Standard Error 1.03 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 47.54 points on a scale | Standard Error 0.75 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 48.61 points on a scale | Standard Error 0.74 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 47.90 points on a scale | Standard Error 0.85 |
| Zopiclone | Mood Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 48.28 points on a scale | Standard Error 0.78 |
Secondary
Sedation Score, as Assessed by the Linear Analogue Rating Scales
The Linear Analogue Rating Scale (LARS) is used as a measure of the subjective effects of psychoactive drugs. Participants mark a series of 10 cm (100 unit line) analogue scales (1-100, 100 = most impaired) relating to dizzy, clumsy, anxious, relaxed, tired, drowsy, alert, energetic, sad, and depressed, indicating their present feeling with regard to a mid-point, representing their usual state of mind before treatment began. The higher the score, the more impaired the participant feels. The Tiredness, Alertness, Energy, and Drowsiness scores are averaged to derive an overall Sedation score.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 53.63 points on a scale | Standard Error 1.12 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 49.02 points on a scale | Standard Error 1.21 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 53.98 points on a scale | Standard Error 1.21 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 53.84 points on a scale | Standard Error 1.14 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 54.21 points on a scale | Standard Error 1.15 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 51.47 points on a scale | Standard Error 1.06 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 54.07 points on a scale | Standard Error 1.18 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 54.54 points on a scale | Standard Error 1.37 |
| Placebo | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 51.77 points on a scale | Standard Error 1.21 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 55.39 points on a scale | Standard Error 1.15 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 54.87 points on a scale | Standard Error 1.16 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 56.40 points on a scale | Standard Error 1.15 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 54.39 points on a scale | Standard Error 1.19 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 54.93 points on a scale | Standard Error 1.12 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 54.68 points on a scale | Standard Error 1.23 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 53.77 points on a scale | Standard Error 1.13 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 51.49 points on a scale | Standard Error 1.06 |
| Eszopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 49.41 points on a scale | Standard Error 1.22 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8.5 hours post-dose, n=89, 87, 90 | 56.93 points on a scale | Standard Error 1.18 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 7.5 hours post-dose, n=89, 87, 90 | 57.00 points on a scale | Standard Error 1.14 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10.5 hours post-dose, n=89, 87, 90 | 55.31 points on a scale | Standard Error 1.12 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 8 hours post-dose, n=89, 87, 90 | 59.21 points on a scale | Standard Error 1.13 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11.5 hours post-dose, n=89, 87, 90 | 51.24 points on a scale | Standard Error 1.2 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9.5 hours post-dose, n=89, 87, 90 | 55.90 points on a scale | Standard Error 1.13 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 9 hours post-dose, n=89, 87, 90 | 56.01 points on a scale | Standard Error 1.1 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 11 hours post-dose, n=89, 87, 90 | 52.79 points on a scale | Standard Error 1.05 |
| Zopiclone | Sedation Score, as Assessed by the Linear Analogue Rating Scales | 10 hours post-dose, n=89, 87, 90 | 55.73 points on a scale | Standard Error 1.21 |
Secondary
Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 68.1 number of substitutions | Standard Error 1.2 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 69.0 number of substitutions | Standard Error 1.16 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 70.9 number of substitutions | Standard Error 1.14 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 70.2 number of substitutions | Standard Error 1.12 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 68.2 number of substitutions | Standard Error 1.09 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 70.9 number of substitutions | Standard Error 1.11 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 70.6 number of substitutions | Standard Error 1.13 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 70.4 number of substitutions | Standard Error 1.16 |
| Placebo | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 71.8 number of substitutions | Standard Error 1.16 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 67.2 number of substitutions | Standard Error 1.13 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 64.7 number of substitutions | Standard Error 1.1 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 66.5 number of substitutions | Standard Error 1.17 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 67.4 number of substitutions | Standard Error 1.13 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 65.2 number of substitutions | Standard Error 1.2 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 68.2 number of substitutions | Standard Error 1.14 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 69.7 number of substitutions | Standard Error 1.17 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 68.1 number of substitutions | Standard Error 1.11 |
| Eszopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 68.0 number of substitutions | Standard Error 1.17 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 66.3 number of substitutions | Standard Error 1.12 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 63.4 number of substitutions | Standard Error 1.09 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 67.8 number of substitutions | Standard Error 1.16 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 65.6 number of substitutions | Standard Error 1.15 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 68.3 number of substitutions | Standard Error 1.16 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 66.5 number of substitutions | Standard Error 1.12 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 64.2 number of substitutions | Standard Error 1.19 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 67.6 number of substitutions | Standard Error 1.1 |
| Zopiclone | Total Number of Attempted Symbol Substitutions, as Assessed by the Digit Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 67.6 number of substitutions | Standard Error 1.13 |
Secondary
Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test
Analysis was performed on the individual assessments conducted at 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind). The Digit Symbol Substitution Test (DSST) is a pen and paper test that consists of rows of blank squares paired with randomly assigned digits (between 0 and 9). Participants are required to substitute each digit with a different nonsense symbol, according to a key printed at the top of the sheet that indicates the nonsense symbol that corresponds to each digit. Participants are given 120 seconds in which to complete the test.
Time frame: 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, and 11.5 hours post-dose (double-blind)
Population: Intent-to-Treat (ITT) Population: all participants who gave informed consent, were randomised, and received at least one dose of double-blind study medication. Only participants who had assessment of the measure the day after double-blind treatment were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 67.9 number of substitutions | Standard Error 1.2 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 68.7 number of substitutions | Standard Error 1.16 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 70.8 number of substitutions | Standard Error 1.14 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 69.9 number of substitutions | Standard Error 1.12 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 67.9 number of substitutions | Standard Error 1.1 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 70.6 number of substitutions | Standard Error 1.11 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 70.4 number of substitutions | Standard Error 1.13 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 70.2 number of substitutions | Standard Error 1.16 |
| Placebo | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 71.5 number of substitutions | Standard Error 1.17 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 66.9 number of substitutions | Standard Error 1.13 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 64.3 number of substitutions | Standard Error 1.1 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 66.2 number of substitutions | Standard Error 1.17 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 67.0 number of substitutions | Standard Error 1.14 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 64.8 number of substitutions | Standard Error 1.21 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 68.0 number of substitutions | Standard Error 1.15 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 69.5 number of substitutions | Standard Error 1.17 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 67.8 number of substitutions | Standard Error 1.11 |
| Eszopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 67.8 number of substitutions | Standard Error 1.17 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8.5 hours post-dose, n=89, 87, 90 | 66.0 number of substitutions | Standard Error 1.13 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 7.5 hours post-dose, n=89, 87, 90 | 63.0 number of substitutions | Standard Error 1.1 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10.5 hours post-dose, n=86, 85, 88 | 67.4 number of substitutions | Standard Error 1.16 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 8 hours post-dose, n=87, 84, 88 | 65.2 number of substitutions | Standard Error 1.16 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11.5 hours post-dose, n=89, 87, 90 | 68.0 number of substitutions | Standard Error 1.12 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9.5 hours post-dose, n=88, 87, 90 | 66.2 number of substitutions | Standard Error 1.12 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 9 hours post-dose, n=88, 87, 90 | 63.8 number of substitutions | Standard Error 1.2 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 11 hours post-dose, n=88, 87, 90 | 67.3 number of substitutions | Standard Error 1.1 |
| Zopiclone | Total Number of Correct Symbol Substitutions, as Assessed by the Digital Symbol Substitution Test | 10 hours post-dose, n=89, 87, 90 | 67.3 number of substitutions | Standard Error 1.14 |